Quantitative imaging of lipid transport in mammalian cells
Juan M. Iglesias-Artola,
Kristin Böhlig,
Kai Schuhmann,
Katelyn C. Cook,
H. Mathilda Lennartz,
Milena Schuhmacher,
Pavel Barahtjan,
Cristina Jiménez López,
Radek Šachl,
Vannuruswamy Garikapati,
Karina Pombo-Garcia,
Annett Lohmann,
Petra Riegerová,
Martin Hof,
Björn Drobot,
Andrej Shevchenko,
Alf Honigmann () and
André Nadler ()
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Juan M. Iglesias-Artola: Max Planck Institute of Molecular Cell Biology and Genetics
Kristin Böhlig: Max Planck Institute of Molecular Cell Biology and Genetics
Kai Schuhmann: Max Planck Institute of Molecular Cell Biology and Genetics
Katelyn C. Cook: Max Planck Institute of Molecular Cell Biology and Genetics
H. Mathilda Lennartz: Max Planck Institute of Molecular Cell Biology and Genetics
Milena Schuhmacher: Max Planck Institute of Molecular Cell Biology and Genetics
Pavel Barahtjan: Max Planck Institute of Molecular Cell Biology and Genetics
Cristina Jiménez López: Max Planck Institute of Molecular Cell Biology and Genetics
Radek Šachl: Academy of Sciences of the Czech Republic v.v.i.
Vannuruswamy Garikapati: Max Planck Institute of Molecular Cell Biology and Genetics
Karina Pombo-Garcia: Max Planck Institute of Molecular Cell Biology and Genetics
Annett Lohmann: Max Planck Institute of Molecular Cell Biology and Genetics
Petra Riegerová: Academy of Sciences of the Czech Republic v.v.i.
Martin Hof: Academy of Sciences of the Czech Republic v.v.i.
Björn Drobot: Institute of Resource Ecology
Andrej Shevchenko: Max Planck Institute of Molecular Cell Biology and Genetics
Alf Honigmann: Max Planck Institute of Molecular Cell Biology and Genetics
André Nadler: Max Planck Institute of Molecular Cell Biology and Genetics
Nature, 2025, vol. 646, issue 8084, 474-482
Abstract:
Abstract Eukaryotic cells produce over 1,000 different lipid species that tune organelle membrane properties, control signalling and store energy1,2. How lipid species are selectively sorted between organelles to maintain specific membrane identities is largely unclear, owing to the difficulty of imaging lipid transport in cells3. Here we measured the retrograde transport and metabolism of individual lipid species in mammalian cells using time-resolved fluorescence imaging of bifunctional lipid probes in combination with ultra-high-resolution mass spectrometry and mathematical modelling. Quantification of lipid flux between organelles revealed that directional, non-vesicular lipid transport is responsible for fast, species-selective lipid sorting, in contrast to the slow, unspecific vesicular membrane trafficking. Using genetic perturbations, we found that coupling between energy-dependent lipid flipping and non-vesicular transport is a mechanism for directional lipid transport. Comparison of metabolic conversion and transport rates showed that non-vesicular transport dominates the organelle distribution of lipids, while species-specific phospholipid metabolism controls neutral lipid accumulation. Our results provide the first quantitative map of retrograde lipid flux in cells4. We anticipate that our pipeline for mapping of lipid flux through physical and chemical space in cells will boost our understanding of lipids in cell biology and disease.
Date: 2025
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DOI: 10.1038/s41586-025-09432-x
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